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Immunotherapy Update: What We’ve Learned

Immunotherapy has been called one of the most significant advances in cancer in decades. While this approach may work in some cancers, it is unclear if or how immunotherapy can be used in NETs.

The Neuroendocrine Tumor Research Foundation (NETRF) has been leading an effort to understand the potential of immunotherapy in NETs. And now we are beginning to see findings emerge. Researchers shared what they’ve learned at a recent NETRF research symposium. One study was published in a peer-reviewed journal days ago.

Three NETRF-sponsored studies, by principal investigators Tim Meyer, MD, PhD, Matthew Kulke, MD, and Daniel Halperin, MD, have been seeking to further understand the immune environment of NETs.

What type of immunotherapy may be best suited for NETs?

Dr. Tim Meyer and colleagues are trying to identify which immune system pathways stop the body from releasing “soldier” cells that can recognize and attack NET cells. “With the support of the NETRF, I have assembled a team of world-leading scientists and clinicians at UCL, London to focus on defining the immune landscape of NETs,” said Dr. Meyer.

How do small intestine tumors respond to immunotherapy?

Matthew H. Kulke, MD, Boston University, Boston, MA

Dr. Matthew Kulke and colleagues have been working on a laboratory model to establish the role of immunotherapies in treating small intestine NETs (SI-NETs). “A better understanding of the immune environment of NETs is vital to establish the role immune therapies will have in this setting,” said Dr. Kulke.

Dr. Kulke’s lab has been assessing the impact of currently available anti-PD-1 immunotherapies, such as nivolumab or pembrolizumab, on NETs. The team has also worked on characterizing circulating immune markers in the blood of patients with NETs, to provide insights on the potential of current and future immunotherapies in this disease. An initial assessment of the immune environment of well-differentiated pNET and SI-NET was recently published in theJournal Pancreas.

Does the immune landscape of pancreatic NETs vary by genomic alteration?

Dr. Daniel Halperin and colleagues have been analyzing the immune environment of advanced pancreatic NETs (pNETs), which they have classified, clinically and genomically, to look for patterns that may predict response. “Any findings can directly inform clinical trials of new drugs for our patients who need them. Our hope is that this work will permit us to move the right drugs into trials for the patients most likely to benefit as quickly as possible,” said Dr. Halperin.

Dr. Halperin’s team has been exploring the relationship between underlying genomic alterations and actionable immune targets to be able to select or combine different classes of therapies. The subclassified perspective of pNETs, based on molecular characteristics, could support increased predictive, prognostic, and therapeutic precision.

NETRF has a great interest in exploring the role of immunotherapy in NETs. “We continue to invest in cutting-edge research to understand what makes tumors such as NETs “cold”, thus unable to be recognized by, or provoke a strong response by the immune system,” said Effie Tzameli, PhD, Director of Research, NETRF. “A comprehensive analysis of the immune environment around a neuroendocrine tumor will help us decipher if and how current immunotherapies fit in the treatment paradigm.”

Comments

I was diagnosed with neuroendocrine carcinoma (MEN1) 4 years ago with with METS to liver and bones. Last month my liver was biopsied and the tissue was tested through Foundation Medicine. I received my results yesterday and there are only a few mutations. Based on the results there appears to be very little hope for immunotherapy at this time. It is amazing that this testing is available to us and possibility of what is on the horizon. My best to all…keep up the good fight.